A simplified approach to the effect kinetics of atracurium.
The combination of the Hill equation, which describes the concentration-effect relation, with the monoexponential function for the terminal decline of plasma concentration, yields a compound time constant, T beta s1/2. This constant is a combination of the terminal elimination half-life (T beta 1/2) and the exponent (s) of the Hill equation and may be used to describe the time course of recovery from neuromuscular block. The constant may be estimated by non-linear curve fitting to f, the effect expressed as fraction of maximal effect, or by linear regression of the logit function of f. The methods were validated using plasma concentration and effect data from seven patients administered atracurium. The two methods utilizing effect data alone yielded values of 4.2 (0.7) min and 4.3 (0.5) min (mean (SEM)), respectively, for T beta s1/2 compared with 4.1 (0.6) min when the constant was calculated using plasma concentration data for T beta 1/2 and curve fitting to the concentration-effect data to determine s. These methods offer an objective measure of the rate of recovery and a means of testing if redistribution or elimination is the primary process in the termination of drug effect.
Graham
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School of Physiology and Pharmacology, University of New South Wales, Australia.
Tsui
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Torda
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TA
D001279:Atracurium / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D008433:Mathematics; D009119:Muscle Contraction / Q000187:drug effects; D013997:Time Factors
D001279:Atracurium